Neuropeptide Y (hereinafter referred to as NPY) is a peptide which consists of 36 amino acid residues and was isolated from porcine brain in 1982. NPY is widely distributed in the central nervous system and peripheral tissues of humans and animals.
It has been reported that NPY possesses a stimulatory action on food intake, an anti-seizure activity, a learning-enhancing action, an anti-anxiety activity, an anti-stress activity, etc. in the central nervous system, and it may be pivotally involved in central nervous system diseases such as depression, Alzheimer's disease, Parkinson's disease. NPY is thought to be involved in cardiovascular diseases, since it induces a contraction of smooth muscles such as blood vessels or cardiac muscles in peripheral tissues. Furthermore, NPY is also known to be involved in metabolic diseases such as obesity, diabetes, hormone abnormalities (Non-patent Document 1). Therefore, an NPY receptor antagonist is expected as medicine for preventing or treating the above mentioned various diseases associated with the NPY receptor.
Six subtypes of NPY receptors have now been identified: Y1, Y2, Y3, Y4, Y5, and Y6 (Non-patent Document 2). It has been suggested that the Y5 receptor is at least involved in the feeding behavior and its antagonist is expected as an anti-obesity drug (Non-patent Document 3).
Hydrazine amide derivatives having structures similar to those of compounds of the present invention and exhibiting an NPY Y5 receptor antagonistic activity are disclosed in Patent Document 1 and Non-patent Document 4.
Patent Document 1 discloses hydrazine amide derivatives having phenyl group substituted with electron-donating group, which correspond to the present compounds having carbocyclyl substituted with alkoxy at Z, but does not disclose hydrazine amide derivatives having phenyl group substituted with electron-withdrawing group described in the present invention.
Patent Document 2 and Non-patent Document 4 disclose compounds, wherein R1 is optionally substituted aryl and X is —CH2-cyclohexylene in the present invention, but do not disclose hydrazine amide derivatives having cyclohexyl described in the present invention.
Patent Documents 3 to 9 disclose compounds having hydrazine amide group, which are useful as an antithrombotic agent. Any one of the compounds, however, is cyclohexane derivative having amino group substituted with heteroaryl carbonyl, and antiobesity effect is not mentioned.    [Non-patent Document 1] Trends in Pharmacological Sciences 1994; 15: 153    [Non-patent Document 2] Trends in Pharmacological Sciences 1997; 18: 372    [Non-patent Document 3] Peptides 1997; 18: 445    [Non-patent Document 4] Bioorganic & Medicinal Chemistry 2004; 12: 4717-4723    [Patent Document 1] WO01037826    [Patent Document 2] JP3445204    [Patent Document 3] US2005020645    [Patent Document 4] WO2004058715    [Patent Document 5] JP2003183286    [Patent Document 6] WO2003016302    [Patent Document 7] WO2003000680    [Patent Document 8] WO2003000657    [Patent Document 9] WO2001074774